Discovery of Ubonodin, an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex.

TitleDiscovery of Ubonodin, an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex.
Publication TypeJournal Article
Year of Publication2020
AuthorsCheung-Lee, WLing, Parry, ME, Zong, C, Cartagena, AJaramillo, Darst, SA, Connell, ND, Russo, R, A Link, J
JournalChembiochem
Volume21
Issue9
Pagination1335-1340
Date Published2020 May 04
ISSN1439-7633
KeywordsAnti-Bacterial Agents, Burkholderia cepacia complex, DNA-Directed RNA Polymerases, Drug Discovery, Humans, Pore Forming Cytotoxic Proteins
Abstract

<p>We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis. The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans, causative agents of lung infections in cystic fibrosis patients.</p>

DOI10.1002/cbic.201900707
Alternate JournalChembiochem
PubMed ID31765515
PubMed Central IDPMC7205569
Grant ListR35 GM118130 / GM / NIGMS NIH HHS / United States
R01 GM107036 / GM / NIGMS NIH HHS / United States